Process for preparing pyridine carboxylic acids



United States Patent fitice 2,694,070 Patented Nov. 9, 1954 PROCESS FORPREPARING PYRIDINE CARBOXYLIC ACIDS No Drawing. Application March 26,1952,

.Serial No. 278,746

11 Claims. (Cl. 260-2955) This invention relates to a process for theoxidation to pyridine carboxylic acids of heterocyclic aromatic nitrogencompounds containing a single pyridine nucleus and having at least oneoxidizable hydrocarbon group, attached to the pyridine nucleus by atleast one carbonto-carbon linkage, and more particularly to theproduction of nicotinic acid from certain compounds of this type.

Pyridine carboxylic acids are useful as intermediates in various organicreactions and in the pharmaceutical field. Of these acids, 3-pyridinecarboxylic acid, i. e. nicotinic acid (Niacin) is a member of thevitamin B complex group and is useful in the enrichment of foods toimprove their nutritional values.

Substituted pyridine and quinoline type compounds of the characterdescribed have been oxidized in the past to pyridine carboxylic acids bya number of methods including oxidation with sulfuric acid at hightemperatures in the presence of a catalyst. Such oxidations, usingsulfuric acid as the sole oxidizing agent, are usually carried out attemperatures between about 305 C. and about 325 C. and even at thesetemperatures and with catalytic acid require considerable time forcompletion of the oxidation reaction, usually fromabout 6 to about 24hours in the presence of a selenium catalyst.

Efforts to provide processes which could be carried out at lowertemperatures and/ or in shorter times, have resulted in the use, forexample, of nitric acid or perchloric acid as oxidizing agents insulfuric acid medium with or without catalysts. These processes, whilesatisfactory from the point of view of rapidity and lower temperatureoperation, nevertheless, require the use and handling of liquidoxidizing agents which are expensive and which from time to time are inshort supply.

I have now found that pyridine carboxylic acids may be prepared rapidly,in good yields, at low temperatures, without resort to auxiliary liquidoxidizing agents, ac-

. cording to my invention wherein l etcrocyclic nitrogen compoundscontaining a single pyridine nucleus and hav-' ing at least oneoxidizable hydrocarbon group attached to the pyridine nucleus by atleast one carbon-to-carbon linkage are oxidized in the liquid phase topyridine carboxylic acids by concentrated sulfuric acid aided by gaseousnitrosyl chloride as an auxiliary oxidizing agent.

As examples of such compounds susceptible to oxidation by the process ofthe present invention there may be mentioned quinoline, isoquinoline,the picolines or methyl pyridines, such as 2-picoline, 3-picoline and 4-picoline, the lutidines or dimethyl pyridines, the collidines, forexample y-collidine or trimethyl pyridine and aldehyde collidine orZ-methyl-S-ethyl pyridine, as well as the methyl quinolines, methylisoquinolines, 5- and 8- nitroquinolines, 5- and 8-hydroxy quinolines,etc.

If the heterocyclic aromatic nitrogen compound of the characterdescribed has an oxidizable hydrocarbon substituent attached to the tiononly, has no unoxidizable substituent group on the pyridine nucleus andhas not more than two additional oxidizable substituents on the pyridinenucleus each of which is in an alpha position, its oxidation willproduce nicotinic acid, either directly in the case of compounds havinga single beta substituent such as 3-picoline, or indirectly in the caseof poly substituted compounds by oxidation of all the substituentsfollowed by decarboxylation of all but a single beta carboxylic acidgroup.

I have found that gaseous nitrosyl chloride (NOCl) which is aninexpensive waste material available in large pyridine nucleus in onebeta posi 2 quantities as a by-product of chlorine manufacture, whenintroduced into a sulfuric acid solution of a heterocyclic nitrogencompound of the character described, at oxida tion temperatures, eitherin the absence of a catalyst or in the presence of a catalyst such as aselenium-contain ing catalyst, acts as an auxiliary oxidizing agent,mark edly to accelerate the rate of the sulfuric acid oxidation. Undercertain conditions its action is that of a supplementary oxidizing agentwhich term, when used herein, means that when such agent is used inconjunction with sulfuric acid in the oxidation of a heterocyclicnitrogen compound, there results a higher rate of oxidation than isobtained by the use of sulfuric acid alone under otherwise identicalconditions, but a rate not higher than the additive oxidation rateattributable to both sulfuric acid and the auxiliary oxidizing agentcombined. Under certain other conditions the nitrosyl chloride acts as apromoter, which term, when used herein, means that the auxiliaryoxidizing agent, when used in conjunction with sulfuric acid in theoxidation of a heterocyclic nitrogen compouud, results in a higher rateof oxidation than the additive oxidation rate attributable to bothsulfuric acid and the added oxidizing agent combined. The term auxiliaryoxidizing agent is used herein as a generic term to denote bothsupplementary oxidizing agents and promoters; and auxiliary oxidizingaction is used to denote the production of any increase, however smallor large, in the oxidation rate over that produced by sulfuric acidalone and includes both supplementary oxidizing action and promoteraction.

An auxiliary oxidizing effect on the sulfuric acid oxidation ofheterocyclic nitrogen compounds is exerted by nitrosyl chloride ineitherthe presence or the absence of a catalyst. Sulfuric acid alone, in theabsence of a catalyst, produces virtually no conversion of heterocyclicnitrogen compounds to pyridine carboxylic acids, even when heated atelevated temperatures of the order of 300 C. for prolonged periods of 10hours or more. With the aid of a selenium type catalyst, completeconversions to pyridine carboxylic acids by sulfuric acid alone requireperiods ranging between about 6 and about 24 hours. Using nitrosylchloride as an auxiliary oxidizing agent accordlng to the process of myinvention and carrylngout the oxidation at temperatures between about240 C. and about 300 C., complete conversions may be obtained in thepresence of a catalyst such as a selenium catalyst, in periods varyingbetween about 30 minutes and about 2 hours depending on the temperatureand rate of nitrosyl chloride input and the particular heterocyclicnitrogen compound oxidized.-

In carrying out the process according to my invention, the heterocyclicaromatic nitrogen base compound, dissolved in concentrated sulfuricacid, is subjected to the action of nitrosyl chloride at elevatedtemperatures in e presence or absence of a catalyst. In a preferredmethod of carrying out the process, the heterocyclic aromatic nitrogenbase compound is mixed with sufficient concentrated sulfuric acid toprovide at least-a slight excess thereof over that required to form thenitrogen base sulfate and to maintain such an excess during the Acatalyst such as selenium or a selenium compound is added to the chargeand, after bringing the charge to oxidizing temperature, the gaseous:NOCl auxiliary oxidizing agent is passed into the hot solution. Flowrate of NOCl may be controlled to provide the optimum or desiredsupplementary or promoter oxidizing action at the particular oxidizingtemperature and the oxidation is continued until the desired conversionof heterocyclic nitrogen compound is attained.

Quantities of catalyst, such as selenium or selenium compound catalyst,used may be between about .5% and about 25% based on the weight of theheterocyclic nitrogen compound used. The sulfuric acid used isconcentrated sulfuric acid, i. e. from about to the ordinaryconcentrated sulfuric acid of commerce (95-96%) being satisfactory.

The temperatures at which the oxidation of the hetero- .cyclic nitrogencompounds described may be carried out using the gaseous nitrosylchloride auxiliary oxidizing agent according to my invention, aresomewhat lower than the optimum temperatures required for oxidation ofthe same heterocyclic nitrogen compound with sulfuric acid alone. Thus,whereas the optimum temperature for oxidizing quinoline to nicotinicacid by means of H280; in the presence of a selenium catalyst liesbetween about 295 C. and about 315 C. and for oxidizing S-picoline liesbetween about 305 C. and about 315 C., the optimum oxidation temperaturewhen using nitrosyl chloride in its auxiliary oxidizing capacity lies inthe neighborhood of 270 C. Suitable temperature ranges within whichsupplemental oxidizing action is exerted by nitrosyl chloride arebetween about 240 C. and about 300 C. At 270 Ci about C. the nitrosylchloride exerts at least a supplementary oxidizing action in the case ofall the heterocyclic nitrogen compounds as defined, and, in the case ofpoly substituted pyridine ring compounds such as quinoline, isoquinolineand Z-methyl-S-ethyl pyridine it exerts a promoter action as well.

The rate at which nitrosyl chloride may be introduced into the chargemay vary. For maximtun oxidation hastening efr'ect however, itpreferably should be introduced as rapidly as it will be completelyabsorbed, but slowly enough so that little if any passes out of thecharge. This rate varies markedly with the stage of the reaction, largerrelative proportions of nitrosyl chloride being generally utilizable inthe early stages of the oxidation than near its completion. In general,I find that introduction of nitrosyl chloride should be made at a rateof at least about 1 part by weight per minute per 100 parts ofheterocyclic nitrogen compound, and may be as high as about parts perminute or higher, at least during the early stages of the oxidation; therate may be decreased somewhat during the later stages if desired whenand if nitrosyl chloride begins to appear in the exit gases. Usually aflow rate between about 2.5 parts and about 10 parts per minute issatisfactory. The total quantity used will vary somewhat depending onthe particular heterocyclic nitrogen compound being oxidized, thetemperature and the rate of introduction of NOCl, but in general shouldbe sufiicient to insure production of the desired supplementary orpromoter action under the conditions of the oxidation. This quantitywill usually lie within the range between about 125 parts and about 650parts per 100 parts by weight of the heterocyclic nitrogen compound.

The oxidation of representative heterocyclic nitrogen bases withsulfuric acid alone proceeds according to the equations set out below(Series A) for quinoline, the picolines and Z-methyl-S-ethyl pyridinerespectively,

A. Theoretical oxidation of nitrogen bases with sulfuric acid Theoxidation of the same representative heterocyclic nitrogen basestheoretically would proceed according to the equations set out below ifall the oxidation were at-' tributable to nitrosyl chloride alone(Series B),

One of the outstanding advantages of the present invention in additionto its inexpensiveness, is the increased rate of oxidation ofheterocyclic nitrogen compounds as described, to pyridine carboxylicacids over that possible with sulfuric acid alone within the temperaturerange defined. The amount of this rate increase depends to some extenton the temperature, to some extent appears to be inherent in thecompounds oxidized.

The increase in reaction rate induced by nitrosyl chloride over the rateof reaction using sulfuric acid alone may readily be demonstrated andmeasured by comparing the results obtained by bubbling nitrosyl chloridethrough the sulfuric acid reaction mixture, with the results obtained bybubbling an inert gas such as nitrogen through an identical oxidationmixture at the same temperature. Any loss of weight incurred in theoxidation mixture through which nitrogen is passed, will be attributableto oxidation by sulfuric acid alone, the nitrogen having no chemicaleffect but reproducing the physical conditions of the nitrosylchloride-treated material by furnishing similar agitation. The loss ofweight is due to loss of CO2,SO2 and water vapor by volatilization asillustrated in the foregoing equations. The weight loss occurring in theoxidation mixture through which nitrosyl chloride is passed will be dueto a combination of sulfuric acid oxidation and nitrosyl chlorideoxidation. A comparison of weight losses at constant conversions andtemperatures in the two types of oxidations gives a measure of the rateincrease attributable to the nitrosyl chloride. Whether such rateincrease represents merely a supplementary oxidizing effect as defined,or represents a promoter (synergistic) effect, may be ascertained bycalculating the percent conversion theoretically ascribable to nitrosylchloride on the basis of the equations set out above, adding thistheoretical conversion to the conversion figure obtained using H2804alone under comparable conditions, and comparing this total with theconversion actually obtained by the combined action of sulfuric acid andthe auxiliary oxidizing agent. Positive diiferences are construed asevidence of promoter action; negative differences correspond toincomplete utilization of the auxiliary oxidizing agent. The degree ofsupplementary oxidizing effect may be ascertained by noting theimprovement in percent conversion obtained when using the auxiliaryoxidizing agent over the percent conversion obtained when using sulfuricacid alone under comparable conditions, all as brought out in thefollowing specific examples which further illustrate my invention. Inthese examples, the figures shown for percent conversion are calculatedfrom the total quantity of heterocyclic nitrogen base used up in thereaction, the resulting reaction product being essentially the acidindicated, together with small quantities of CO2 and ammoma.

EXAMPLE 1 I Quinoline was oxidized to nicotinic acid using sulfuric ac das the primary oxidizing agent and nitrosyl chloride as auxiliaryoxidizing agent at about 270 C.

@QQQMQ The p aratu used as a -seek; equipped with a as n t tube. thmometer. hermo ouple well and. ah: eeeds se he flask heated ya quartzhemisnheni a mantle and mper tu e controll d by: than mocouple connectedentire apparatus (mantle and flask) was placed in a balance in a mannersuch that smallweight changes in the charge were readily detectable.

In c ryin ut h un, t flask wa h rged. with 2 parts of selenium as caalyst and 5,16% solution of quinol'ine 95%. clgargg was brought rapidlyto, op 05 s f utie acid; The. ratin tempenat re n 1,5 t m nht s; wh reitwasme ntains Nitrosyl chloride. at room, temperature, Qabout- 25.(1.). was then passed into the hot solution at a rate of, 0.5 liter (.02mol) per minute or 1.3 parts by weight per minute. As the oxidation;progressed the weight of the charge decreased due to evolution ofgaseous products tion o he: quino ii e. Weight. loss s were re: cordedperiodically: and at the same. time samplesxof the charge were analysedfor conversion of the qu-inoiine to nicotinic acid and the resultsrecorded.

Progress of) the, oxidation is shown in Table 1A below.

Table 1A Av run carried-out in a. manner: identical in all respects tothe above except that nitrogen waspassedthrough' the charge inplace ofnitrosyl chloride, gayethe results shown. in Table 1B: below.

Table 1B [Weight loss during oxidation oi quiHO1inB.,With,H2sQL at. 270.

' introduction 0 f N2 at 0 .'5 literper lnlnute],

gas. was, oneliter; per. minute (246 parts, by. weight; per weightminute) Wltli. the results, listed; m, Table. 3A below. Elapsed Time,Minutes Tabla} 3 53; Weight loss'andconversion ofquinoli'ne duringoxidation with HtSOi 15v v at 270 0. supplemented by NQOltlntroduced at1 liter per minute] 30 n v. 5. 60' v l Wright P t 120- .t e ercen 210- iElap-sed-Tme"Mmutes -Izoss;Parts Conversion" in 5, i .l 5

In Table 1C below, the conversion of quinoline by 1?? I 5%? sulfuricacid alone, and that. theoretically ascribable to 1. nitrosyl chloridealone under comparable conditions as 6m to 14 a 39.15:, calculated fromthe-equatronsam; C(31l1mIl'S3.-al1d-i4; are.

listed and the totals of-thesetwo effects are-listedi Theactual-conversion found is also listed together-with the improvement-inconversion oven-HzSOnalone andover the theoretical total of H2SO4- and initrqsyl; chloride.

Table 1C Conversion in'percentmi qulnoline during oxidation at-.:270 O.with,

HgSOl alqneand with-introductionof N001 at 0.5 lltepiaet minute] TotalImprove- Improve-- Time, 5 8 9 5 338 H2SO Actual ment over ment overMin. Found No.01, Total; 1118.04. Theoreti- Theory f alone; calTotal.

l5 14 7. 5 21. 5 38. 5 31.0 +17 30 28. 5 15 43. 5 59. 3 44. 3 +15. 8 4s22. 5;. 65. 5; 73.8 51. a +8.3 57 30 87 84. 0 54 -3. 0 71. 5 85.0

with 29. p r s of a 10 6 exAMPItE; 2.,

Another 0.1- quiholi'ne; to nicotinicacid was;

carried out in a manner identical with that employed in toa1pgqtgnfiomgtemcgnmoucn The! 5; Example 1 except that the: oxidationtemperature was 2.4.0, C.,, with the. results. listed. in Table. 2Abelow...

Tizbl'e" 221 i Weight 1 Percent Elapsed Time Minutes Loss,,1 artsConversion the conversion of quiholine: by that theoreticallyascribabl'eto Il'n 'Fa-ble 28 below; sulfuric acid alone and 20:nitrosyl chloride under comparable conditions as calcul'ated tom theequations: in columns 3 and 4', are. listed;

and the totals of these two effects are listed. The actualconversionfound is also listedtogether with improvements in conversion over H2504alone and over the theoretical-r total? of: H2594. andi nitrosylchloride.

Table. 2B

[ on ersion nt nercent: at quino line; d'urin 7 H1804 alone and withintroduction of NO 1 at 0.5 liter per minute].

mi ditions of then'un NOCllexerts. asupplementary oxidizing- It will be,observed from Table 28' that under the con.-

action, although noobservable promoter action.-

EXAMPLE Another. oxidation of quinoline to nicotinic. acid. was, with.45: carried. qutin. a. manner. identical. with that employed 1n .EXample1..exceptthat the rate offintrodnction ofNoC'I.

Ina--runcarried-out in a manner identical in all re-- SQElJ-S? with:hat; described. above: except: that. nitrogen 65: gas was'-,in. mduced;;instead-of;- nitrosyl chloride, the re-.

It will be observed from Table. 1,6; that under; the con,-

ditions of the; NQCl exerte a; significa p ien nr he y aeewt. sfexidatentan up lem nt ry dizina eti nhro ghout: he; n ite; course of theoxidation.

listed-andatheatotalssuits. listed. nrTable; 3B wereobtained;

.'Z"al2le--3B [We lghtloss duliuepxidationnf.quinoline with H2804-at.270 C; withlntroduetio'n ,of N at 1 litenper minute] Weight, PercentElapsed Time Hours Loss, Parts Conversion In Table 30 below, sulfuricacid alone and nitrosyl chloride .alone the conversion of. quinoline bycalculated from the ct theseatwo-efiectsare listed-.- The oxidationat:'240 with that. theoretically ascribable to i under comparable:conditions equations in,columns 3 and 4,- areactual conversion found isalso listed together with the improvement in conversion over H 2SO4alone and over the theoretical total of H250; and mtrosyl chloride.

Table 36 [Conversion in percent of quinoline during oxidation at 270 C.with 11:30.; alone and with introduction or NOCl at. 1 liter per minute]Total Improve- Improveits? an a te at n Min. o a z 4 core Thewy FoundTheory alone cal Total The data listed in Table 3C indicate that underthe conditions of the run NOCl exerts a promoter action in the earlystages of the oxidation and exerts a supplementary oxidizing actionthroughout the course of the oxidation.

EXAMPLE 4 Still another oxidation of quinoline to nicotinic acid wascarired out, in a manner identical with that employed in Example 1except that the oxidation temperature was 300 C. with the results listedin Table 4A In a comparable run carried out at the same temperature asthe above and in all respects identical with that described above exceptthat nitrogen gas was introduced instead of nitrosyl chloride, at a rateof 1 liter per minute (instead of 0.5 liter per minute as in the aboverun) the results listed in Table 48 below were obtained.

Table 48 [Weight loss during oxidation of quinoline with H1804 at 300 C.with introduction of N; at 1 liter perminute] W h Elapsed Time MinutesLossi fia its ogfiilii ion In Table 4C below, the conversion ofquinoline by sulfuric acid alone and that theoretically ascribabie tonitrosyl chloride alone under comparable conditions as calculated fromthe equations in columns 3 and 4, are listed and the totals of these twoeffects are listed. The actual conversion found is also listed, togetherwith the improvement in conversion over H2504 alone and over thetheoretical total of H2804 and nitrosyl chloride.

Table 4C I [Conversion in percent of quinoline during oxidation at 300C. with H2804 alone and with introduction of NOCl at 0.5 liter perminute] Total Improve Improveas o a 2 4 core Theory Found Theory alonecal Total 9. 5 35 44. 5 i2. 5 7. 5 2 19 51. 5 70. 5 7D. 7 19.2 +0. 2 28.5 55. 5 S4. 0 84. 2 28. 7 +0. 2 33 60 98 91 31 -7 was introduced at 1liter per minute.

The above table indicates that NOCI exerts a supplementary oxidizingaction under the conditions of the run at 300 C. This temperatureappears to be about the threshold temperature at or below which somepromoter action may also be expected.

EXAMPLE 5 3-Picoline was oxidized to nicotinic acid in a manneridentical in all respects to that described for quinoline under Example1 except that 865 parts of a 6.5% solution of B-picoline in sulfuricacid was used as the charge and that NOCl was introduced at the rate of1 liter per giilnute. The results of this run are listed in Table 5A eow.

Table 5.4

[Weight loss and percent conversion of S-picoline during oxidation withB31810: }at 270 C. supplemented by NOCl introduced at 1 liter per m u eWeight Percent Elapsed Time, Minutes Loss, Conver- Parts sion 15 7(gain) 11.7 30 10 22. 7 60 10 43. 8

In a run carried out in a manner identical in all respects to thatdescribed above except that nitrogen was introduced instead of nitrosylchloride, the results listed in Table 5B below were obtained.

Table 58 [Weight loss and percent conversion of 3-picoline duringoxidation with H3804 at 270 0. with introduction of N1 at 1 liter perminute] Weight Percent Elapsed Time Hours Loss, Paits Conversion InTable 5C below, the conversion of 3-picoline by 'sulfuric acid alone,and that theoretically ascribable to nitrosyl chloride under comparableconditions as calculated from the equations in columns 3 and 4, arelisted and the totals of these two eiiects are listed. The actualconversions found in each case are also listed together withimprovements in conversion over H2504 alone and over the theoreticaltotal of H250; and nitrosyl chloride.

Table 5C [Conversion, in percent, of 3-picolino during oxidation at 270C. with H1804 alone and with introduction of NOCl at 1 liter per minute}Tot Improve- Improve- Time, E 8 3 5 HzS 04+ Actual ment over ment overMin. Theo i N 001, Total H Theoretiry Theory alone cal Total The abovedata indicate that, under the conditions of the run NOCl exerts asupplementary oxidizing action.

on the oxidation of 3-picoline, but no promoter action.

EXAMPLE 6 3-Picoline was oxidized to nicotinic acid in a manneridentical in all respects to that described for quinoline under Example1 except that 875 parts of a 6.5% solution of 3-picoline in sulfuricacid was used as the charge and the oxidation was carried out at 300 C.and N001 this run are listed in Table 6A below.

The results of 1' Table 6A [Wfiight loss and percent conversion of3-picoline during oxidation with 04 at 300 C. supplemented by N]introduced at 1 liter per minute] Weight Percent Elapsed Time MinutesLoss,,Parts Conversion In a run carried out in a manner identical in allrespects with that described above except that nitrogen gas wasintroduced instead of nitrosyl chloride, the results listed in Table 68below were obtained.

Table 6B [Weight loss and percent conversion during oxidation of3-picoline with H 8 04 at 300 C. with introduction of N: at 1 liter perminute] Weight Percent Elapsed Tune Hours Loss, Parts Conversion Table6C [Conversion. in percent, of 3-picoline during oxidation at 300 C.with H 04 alone and with introduction of N 0 G1 at 1 liter per minute]Total Improve- Improve- 0 a z 4 core Theory Found Theory alone cal TotalThe above table indicates that under the conditions of the run, NOClexerts an appreciable supplementary oxidizing eifect on the H2804oxidation of 3-picoline but no promoter action.

7 EXAMPLE 7 Isoquinoline was oxidized to cinchomeronic acid in a manneridentical in all respects to that described for quinoline under Example1 except that 890 parts of a 5.15% solutionof isoquinolineinsulfurica'cid was used as the charge and the NOCl was introduced atthe rate of 1 liter per minute. Results of this run are given in Table7A below.

Table 7A [Weight loss and percent conversion ofisoquinoline duringoxidation with H 80; ]at 270 C. supplemented by N 001 introduced at 1liter per mm e Y 10 Table 17B [Weight loss and percent conversionoi-isoquinoline during oxidation with Hrs 04 at 270 C. with introductionof N2 at 1 liter per minute] Weight,

Percent Elapsed Time Hours Loss, Parts Conversion [Oonverslom inpercent, of isoquinoline during oxidation at 270 C. with H 804 alone andwith introduction of NO 01 at 1 liter per minute] Total Improve-Improve- Time, 5 01 gig Hrs 04+ Actual ment over ment over Min. F 6 NOCTotal mso. Theoretieory oun Theory alone cal Total The above tableindicates that under the conditions of the run NOCl exerts aconsld'erable supplementary oxidizing action, and some promoter actionon the H2504 oxidation of isoquinoline.

EXAMPLE 8 Z-methyl-S-ethyl pyridine (aldehyde collidine) was oxidized tonicotinic acid in a manner identical in all respects to that describedfor quinoline in- Example 1, except that 875 parts of a 5% solution ofZ-methyl-S- ethyl pyridine in sulfuric acid was used as the charge.

Results of this run are given in Table 8A below.

Table 8A [Weight loss and percent conversion or 2-methyl-5-cthylpyridinoduring oxidation with H2804 at 270 C. supplemented by N001 introduced at0.5 liter per minute] Weight Percent Loss, Parts Conversion ElapsedTimaMinutes moulmhco Oocnoul oooenww l"??? Table 83 [Weight loss andpercent conversion during oxidation of 2-methyl 5-ethyl pyirlidinle withH98 04 at 270 C. with introduction of N: at 0.5 liter per in ute I IWeight, Percent w l ht P t Elapsed Hours Loss, Parts Conversion e gercen Elapsed Time Minutes Loss, Parts Conversion In Table 8C below, theconversion of 2-methyl-5- In a run carried out in a manner identical inall respectsito that described above except that nitrogen was introducedinstead of nitrosyl chloride, the results listed in Table 7B below wereobtained.

ethyl pyridine by sulfuric acid alone, and that theoretically ascribableto nitrosyl chloride alone as calculated from the equations in columns 3and 4, are listed and the totals of these two eflects are listed. Theactual conversions found are also listed, together with improvements ini1 conversions over H2504 alone and over the theoretrical total of H2804and nitrosyl chloride.

Table 8C [Conversion. in percent, of 2-methyl-5-ethy1 pyridine duringoxidation at The above table indicates that under the conditions of therun, NOCl exerts a considerable supplementary oxidizing action andappreciable promoter action on the H2504 oxidation of 2-methyl-5-ethylpyridine.

While the above describes .the preferred embodiments of my invention, itwill be understood that departures may be made therefrom within thescope of the specification and claims.

l. A process for preparing pyridine carboxyhc acids which comprisessubjecting a heterocyclic nitrogen compound containing a single pyridinenucleus, selected from the group consisting of quinoline, alkylquinolines, isoquinoline, alkyl isoquinolines, 5- and S-hydroxyquinolines, 5- and S-nitroquinolines and the alkyl pyridines, dissolvedin concentrated sulfuric acid to the action of nitrosyl chloride at atemperature between about 240 C. and about 300 C. in the presence ofbetween about 0.5% and about 25 by weight, based on the weight of thenitrogen compound of a selenium-containing catalyst to convert theheterocyclic nitrogen compound to a pyridine carboxylic acid thequantity of sulfuric acid used being sufficient to provide at least aslight excess thereof over that required to form the nitrogen basesulfate, and to maintain such an excess during the oxidation reaction.

2. The process according to claim 1 wherein the heterocyclic nitrogencompound is isoquinoline.

3. A process for preparing pyridine carboxylic acids which comprisessubjecting a sulfate of a heterocyclic nitrogen compound containing asingle pyridine nucleus, selected from the group consisting ofquinoline, aikyl quinolines, isoquinoline, alkyl isoquinolines, 5- and8- hydroxy quinolines, 5- and S-nitroquinolines and the alkyl pyridines,dissolved in concentrated sulfuric acid r to the action of nitrosylchloride at a temperature between about 240 C. and about 300 C. in thepresence of between about 0.5% and about 25% by weight, based on theweight of the nitrogen compound, of a seleniumcontaining catalyst toconvert the heterocyclic nitrogen compound to a pyridine carboxylic acidthe quantity of sulfuric acid used being sufiicient to provide at leasta slight excess thereof over that required to form the nitrogen basesulfate, and to maintain such an excess during the oxidation reaction.

4. A process for preparing pyridine carboxylic acids which comprisessubjecting a heterocyclic nitrogen'compound containing a single pyridinenucleus, selected from the group consisting of quinoline, alkylquinolines, isoquinoline, alkyl isoquinolines, 5- and 8-hydroxyquinolines, 5- and 8-nitroquinolines and the alkyl pyridines, dissolvedin concentrated sulfuric acid to the action of nitrosyl chloride at atemperature between about 240 C. and about 300 C. in the presence ofbetween about 0.5% and about 25 by weight. based on the weight of thenitrogen compound of a selenium-containing catalyst for a period betweenabout 30 minutes and about 2 hours the quantity of sulfuric acid usedbeing sufficient, to provide at least a slight excessthereof over thatrequired to form the nitrogen base sulfate, and to maintain such anexcess during the oxidation reaction.

5. The process of claim 1 wherein the heterocychc nitrogen compound isquinoline.

6. The process of claim 1 wherein the heterocychc mtrogen compound is3-picoline.

7. The process of claim 1 wherein the heterocychc nitrogen compound is2-methyl-5-ethyl pyridine.

8. In a process for accelerating the sulfuric acid oxidation ofheterocyclic nitrogen compounds containing a single pyridine nucleusselected from the group consisting of quinoline, alkyl quinolines,isoquinoline, alkyl 1S0- quinolines, 5- and 8-hydroxy quinolines, 5- andS-nitroquinolines and the alkyl pyridines, the steps which comprisedissolving said heterocyclic nitrogen compound and between about 0.5 andabout 25 by weight, based on the weight of the nitrogen compound aseleniumcontaining catalyst in concentrated sulfuric acid, andsubjecting the resulting solution in the liquid phase to the action ofgaseous nitrosyl chloride at temperatures between about 240 C. and about300 C. to effect conversion of heterocyclic nitrogen base to pyridinecarboxylic acid the quantity of sulfuric acid used being sufficient toprovide at least a slight excess thereof over that required to form thenitrogen base sulfate, and to maintain such an excess during theoxidation reaction.

9. A process for producing an acceleration of the selenium catalyzedsulfuric acid oxidation of quinoline, greater than that theoreticallyascribable to the combined action of the oxidizing agents used, whichcomprises subjecting said quinoline, dissolved in concentrated sulfuricacid, and in the presence of between about 0.5% and about 25% by weight,based on the weight of the quinoline, of a selenium-containing catalyst,to the action of nitrosyl chloride at a temperature of about 270 C. fora period of at least about 30 minutes, the quantity of sulfuric acidused being suflicient to provide at least a slight excess thereof overthat required to form quinoline sulfate and to maintain such an excessduring the oxidation reaction.

10. A process for producing an acceleration of the selenium catalyzedsulfuric acid oxidation of isoquinoline, greater than that theoreticallyascribable to the combined action of the oxidizing agents used, whichcorn prises subjecting said isoquinoline, dissolved in concentratedsulfuric acid, and in the presence of between about 0.5% and about 25%by weight, based on the weight of the isoquinoline, of aselenium-containing catalyst, to the action of nitrosyl chloride at atemperature of about 270 C. for a period of at least about 30 minutes,the quantity of sulfuric acid used being sufficient to provide at leasta slight excess thereof over that required to form isoquinolinc sulfateand to maintain such an excess during the oxidation reaction.

1l. A process for producing an acceleration of the selenium catalyzedsulfuric acid oxidation of 2-methyl-5- ethylpyridine, greater than thattheoretically ascribable to the combined action of the oxidizing agentsused, which comprises sub ecting said 2-methyl-5-ethylpyridine,dissolved 1n concentrated sulfuric acid, and in the presence of betweenabout 0.5 and about 25 by weight, based on the weight of the2methyl-5-ethylpyridine, of a selen um-containing catalyst, to theaction of nitrosyl chloride at a temperature of about 270 C. for aperiod of at least about 30 minutes, the quantity of sulfuric acid usedbeing sufiicient to provide. at least a slight excess thereof over thatrequired to form Z-methyl-S-ethylpyridine sulfate and to maintain suchan excess during the oxidation reaction.

No references cited.

1. A PROCESS FOR PREPARING PYRIDINE CARBOXYLIC ACIDS WHICH COMPRISESSUBJECTING A HETEROCYCLIC NITROGEN COMPOUND CONTAINING A SINGLE PYRIDINENUCLEUS, SELECTED FROM THE GROUP CONSISTING OF QUINOLINE, ALKYLQUINOLINES, ISOQUINOLINE, ALKYL ISOQUINOLINES, 5- AND 8-HYDROXYQUINOLINES, 5- AND 8-NITROQUINOLINES, AND THE ALKYL PYRIDINES DISSOLVEDIN CONCENTRATED SULFURIC ACID TO THE ACTION OF NITROSYL CHLORIDE AT ATEMPERATURE BETWEEN ABOUT 240* C. AND ABOUT 300* C. IN THE PRESENCE OFBETWEEN ABOUT 0.5% AND ABOUT 25% BY WEIGHT, BASED ON THE WEIGHT OF THENITROGEN COMPOUND OF A SELENIUM-CONTAINING CATALYST TO CONVERT THEHETEROCYCLIC NITROGEN COMPOUND TO A PYRIDINE CARBOXYLIC ACID THEQUANTITY OF SULFURIC ACID USED BEING SUFFICIENT TO PROVIDE AT LEAST ASLIGHT EXCESS THEREOF OVER THAT REQUIRED TO FORM THE NITROGEN BASESULFATE, AND TO MAINTAIN SUCH AN EXCESS DURING THE OXIDATION REACTION.